LAUSR

Our comprehension of lymphatic biology, as well as our ability to contemplate therapeutic amelioration of human lymphatic diseases, depends heavily upon insights into the central biology of the lymphatic endothelial cell. In the current issue of Lymphatic Research and Biology, two of the articles touch significantly upon this topic. Wang et al. have chosen to explore the effects of mechanical stress on lymphatic endothelial cells (LECs) in tissue culture. They propose that the large body of published literature related to the LECs is derived from work in which these cells are grown under static conditions, thereby potentially eluding the molecular phenotype of the LEC, and its behavior, in the context of lymphedema. Accordingly, in their study, they exposed the cultured cells to stretch; under these conditions, the cells retained a mature phenotype; however, under conditions of extreme mechanical stress, proliferation of the LECs was significantly enhanced, accompanied by a significant increase in Prox1 expression. The authors interpret their observations as reflecting a lymphedematous cellular phenotype with the feature of enhanced lymphangiogenesis. In a parallel manuscript in this issue, Nizamutdinova and colleagues have examined histamine as an endotheliumderived relaxing factor in aged mesenteric lymphatic vessels. The mesenteric vasculature of rats at 9and 24-months of age were procured and pharmacologically manipulated with inhibitors of nitric oxide and histamine, respectively. The data derived from these investigations constitute the first demonstration of an enhanced functional role for histamine as an endothelial-derived relaxing factor in aging lymphatic vessels; this effect is observed in parallel with a diminished role for nitric oxide in the regulation of the vascular responses to increased flow. Taken together, these manuscripts advance our ability to interrogate lymphatic cellular and vascular function and represent concepts that should be increasingly emphasized as tissue culture and vascular functional studies are employed to comprehend the lymphatic responses to health and disease.